Acetic Acid → HCID 86740524, compound

HRID 845797Notes

Reaction equation

HRID 845797 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[NH:18][CH:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][NH:27][C:28]3[N:33]=[CH:32][CH:31]=[CH:30][N:29]=3)[CH2:21][CH2:20]2)=[CH:4][CH:3]=1.[C:34]([O:37][C:38](=[O:40])[CH3:39])(=[O:36])[CH3:35].[C:41]([OH:44])(=[O:43])[CH3:42]>>[C:38]([OH:37])(=[O:40])/[CH:39]=[CH:42]/[C:41]([OH:44])=[O:43].[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[NH:18][CH:19]2[CH2:24][CH2:23][N:22]([CH2:25][CH2:26][N:27]([C:28]3[N:29]=[CH:30][CH:31]=[CH:32][N:33]=3)[C:34](=[O:36])[CH3:35])[CH2:21][CH2:20]2)=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 7918Acetic AnhydrideHCID 13588090HCID 13588090, compound

Product 1

HCID 86740524HCID 86740524, compoundYield 16.5%

Procedure

A mixture of 4.5 parts of 1-[(4-fluorophenyl)methyl]-N-[1-[2-[(2-pyrimidinyl)amino]ethyl]-4-piperidinyl]-1H-benzimidazol-2-amine, 15 parts of acetic acid anhydride and 140 parts of acetic acid was stirred and refluxed overnight. The reaction mixture was evaporated. The residue was taken up in water and the whole was alkalized with ammonium hydroxide. The product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by HPLC over silica gel using a mixture of methylbenzene and ethanol (90:10 by volume) as eluent. The second fraction was collected and the eluent was evaporated. The residue was converted into the (E)-2-butenedioate salt in methanol. The salt is filtered off and dried, yielding 1.2 parts (16.5%) of N-[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]-N-(2-pyrimidinyl)acetamide (E)-2-butenedioate (1:2); mp. 191.1° C. (compound 99).

Workup

  1. temperaturerefluxed overnight
  2. customThe reaction mixture was evaporated
  3. extractionThe product was extracted with dichloromethane
  4. customThe extract was dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by HPLC over silica gel using
  8. additiona mixture of methylbenzene and ethanol (90:10 by volume) as eluent
  9. customThe second fraction was collected
  10. customthe eluent was evaporated
  11. filtrationThe salt is filtered off
  12. customdried

Sources & evidence

ORD record
ord-9392c64f410741fcb63b9dd78257655c
Source dataset
uspto-grants-1988_07
Patent number
US04760074

Reaction notes

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